Click Here to
Subscribe
Breaking
News, Updates,
& More
Stay Up
to Date

A Phase 2 Study of Durvalumab, a PD-L1 Inhibitor, and Olaparib in Recurrent Ovarian Cancer

Conference Correspondent  - ESMO 2018

Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, has previously shown clinical activity in subsets of patients with recurrent ovarian cancer.1 Based on the hypothesis that olaparib may complement the antitumor activity of immune checkpoint inhibitors like durvalumab, clinical trials have been undertaken to evaluate the safety and efficacy of the combination in recurrent ovarian cancer. In a previous phase 1 study, Lee and colleagues reported safety data and the recommended phase 2 dose of durvalumab + olaparib.2 Here, the same investigators report the safety data and clinical activity in the phase 2 cohort.3

Thirty-five patients with performance scores ranging from 0 to 1, good end-organ function, and biopsiable disease received at least 1 cycle of treatment. Each cycle consisted of the recommended phase 2 dose of 300 mg oral olaparib, twice daily, and 1500 mg intravenous durvalumab on day 1 of each 28-day cycle. The primary objective was to estimate clinical activity using Response Evaluation Criteria in Solid Tumors 1.1 objective response rate and a 2-stage design targeting 35 evaluable patients. Secondary objectives included progression-free survival and safety as assessed by Common Terminology Criteria for Adverse Events (version 4.0). Tissue and blood samples were collected both during pretreatment and on therapy, at cycle 1, day 15 and cycle 3, day 1.

The median age of patients in this study was 67 years (range 40-85 years), and 6 (17%) were germline BRCA mutation carriers (BRCAm), whereas 29 (83%) were BRCA wild type (BRCAwt). Thirty patients (86%) had platinum-resistant recurrent disease, and the median number of prior therapy regimens was 3.5 (range 1-16).

Of 34 evaluable patients (6 BRCAm, 28 BRCAwt), 5 partial responses (PRs) were observed (15% response rate, median 11 months [range 6.5-23 months]). Of those patients with PR, 2 patients were BRCAm (1 with platinum-resistant disease [8.5 months] and 1 with platinum-sensitive disease [11+ months]) and 3 patients were BRCAwt (2 with platinum-resistant disease [23 and 14+ months] and 1 with platinum-sensitive disease [6.5months]). Twenty patients (57%) had stable disease (SD) of ≥4 months (median 6.5 months [range, 4-12.5 months]), yielding a 37% clinical benefit rate (PR + SD ≥4 months).

High-grade (≥grade 3) adverse events included anemia (26%) and lymphopenia (14%). Three patients required a dose reduction of olaparib due to grade 3 anemia (n = 1), grade 3 atrial fibrillation (n = 1), and recurrent grade 2 nausea refractory to supportive care (n = 1). Biomarker analysis is ongoing, including tumor mutational burden, PD-L1/tumor-infiltrating lymphocyte expression, and STING pathway evaluation.

The results presented here suggest that the combination of durvalumab and the PARP inhibitor olaparib was well-tolerated and had clinical activity in a subgroup of heavily pretreated BRCAwt patients with ovarian cancer. Ongoing biomarker evaluation will further characterize the subset of patients who will benefit most from this combination.


References

  1. Lorusso D, et al. Drug Des Devel Ther. 2018;12:1501-1509.
  2. Lee J-M, et al. ASCO 2016. Abstract 3015.
  3. Lee J-M, et al. ESMO 2018. Abstract 936PD.
Related Items
A Meta-Analysis to Evaluate the Risk for Fatigue in Patients Treated with Olaparib for Advanced Cancer
Conference Correspondent  published on October 22, 2018 in ESMO 2018
A Phase 1b and Randomized Phase 2 Trial of Pazopanib with or Without Fosbretabulin in Advanced Recurrent Ovarian Cancer
Conference Correspondent  published on October 22, 2018 in ESMO 2018
The Efficacy of Apatinib Treatment for Advanced Ovarian Cancer After Second-Line Chemotherapy Failure
Conference Correspondent  published on October 22, 2018 in ESMO 2018
Oregovomab and Nivolumab as a Combinatorial Immunotherapy Strategy for Recurrent Epithelial Ovarian Cancer
Conference Correspondent  published on October 22, 2018 in ESMO 2018
Maintenance Olaparib Following Platinum-Based Chemotherapy in Newly Diagnosed Patients with Advanced Ovarian Cancer and a BRCA1/2 Mutation: Results from the Phase 3 SOLO1 Trial
Conference Correspondent  published on October 21, 2018 in ESMO 2018
A Phase 2 Trial of Combination Nivolumab and Bevacizumab in Recurrent Ovarian Cancer
Conference Correspondent  published on October 21, 2018 in ESMO 2018
Association of PD-L1 Expression with Clinical Response to Pembrolizumab in Patients with Advanced Recurrent Ovarian Cancer
Conference Correspondent  published on October 21, 2018 in ESMO 2018
A Phase 1/2 Study of Chemo-Immunotherapy with Durvalumab and Pegylated Liposomal Doxorubicin (PLD) in Platinum-Resistant Recurrent Ovarian Cancer
Conference Correspondent  published on October 20, 2018 in ESMO 2018
Meta-Analysis of PARP-Inhibitor–Associated Gastrointestinal and Hepatic Toxicities
Conference Correspondent  published on October 20, 2018 in ESMO 2018
Clinical Characteristics of Ovarian Cancer Relapse in BRCA1/2 Germ-Line Mutation Carriers and Noncarriers
Conference Correspondent  published on October 20, 2018 in ESMO 2018
Last modified: October 20, 2018